The migration of activated endothelial cells through a vitronectin-rich provisional matrix is critical to the formation of new blood vessels during angiogenesis and is dependent on adhesion receptors containing alphav integrins (such as alphavbeta3 which binds to vitronectin). Peptide and antibody inhibitors of alphavbeta3 integrin inhibit tumor growth in vivo.
Angiogenesis is typically limited in a normal adult to the placenta, ovary, endometrium and sites of wound healing. However, angiogenesis, or its absence, plays an important role in the maintenance of a variety of pathological states. Some of these states are characterized by neovascularization, e.g., cancer and tumorigenesis, e.g., endometriosis, diabetic retinopathy, glaucoma, glomerulonephritis, and age related macular degeneration. Others, e.g., stroke, infertility, heart disease, e.g., restenosis, ulcers, and scleroderma, are diseases of angiogenic insufficiency. Therefore, there is a need to identify nucleic acids encoding proteins involved in the regulation of angiogenesis and tumorigenesis, to identify, e.g., modulators of angiogenesis, as well as new therapeutic and diagnostic applications.